Table 1.
Key cytokines involved in atopic dermatitis
| Cytokine | Cellular origin/stimulus | Cytokine receptor | Cell type(s) expressing the receptor | Overall function/AD MOA, itch, pain | References |
|---|---|---|---|---|---|
| IL‐4 | ILC2, CD4+ T cells, eosinophils, basophils | IL‐4Rα, γC | Sensory neurons | Development of Th2 cells; ↓EDC molecules; ↑itch, IL‐31, MHC class II; activate sensory neurons | 22, 24, 40, 41, 114, 141 |
| IL‐13 | Mast cells, basophils, eosinophils, ILC2, CD4+ T cells | IL‐4Rα, IL‐13rα1 | Sensory neurons | Induce Th2 response; ↑IL‐31, TRPA1, branching, itch; ↓filaggrin; activate sensory neurons | 2, 24, 40 |
| IL‐22 | Mast cells | IL‐10 family | ↓Filaggrin, claudin‐1; ↑GRP, TSLP, IL‐33, itch | 29, 30 | |
| IL‐31 | T cells, DCs, Th2 cells, skin cells, eosinophils, basophils, mast cells | IL‐31R, OSMR | DRGs, sensory nerves, leukocytes, keratinocytes | ↑NKB, itch, BNP, branching; ↓filaggrin; stimulate sensory neurons via TRPA1 | 19, 32, 35, 40, 80 |
| TSLP | Keratinocytes/in response to proteases and bacteria | TSLPR, IL‐7Rα | Sensory nerves, ILC2 | ↑IL‐31, IL‐33, itch; activate sensory neurons via TRPA1, T cells, DCs, mast cells; stimulate ILC2; link innate and adaptive immune responses | 2, 10, 11, 39, 50, 142 |
| IL‐33 | Keratinocytes, macrophages, DCs | IL‐33R, ST2 | Astrocytes, mast cells, ILC2 | ↑IL‐4, IL‐13, IL‐33, TNF‐α, CXCL8, PGD2, itch | 44, 49, 50 |
| IL‐17 | CD4+ T cells | IL‐17RA | Skin cells, ILC2 | ↑GM‐CSF | 48, 50, 54 |
| IL‐25 | Keratinocytes | IL‐17RB | ILC2 | ↑IL‐13 | 49, 50 |
| IL‐18 | Keratinocytes, macrophages, DCs | IL‐18R | Th1 cells | ↑IFN‐γ, ↑IL‐4, chemokines, inflammation, skin barrier dysfunction, skin pain | 52 |
| GM‐CSF | Keratinocytes, T cells, B cells, NK cells, monocytes/macrophages, fibroblasts, mast cells | GM‐CSFRα | Keratinocytes | Induces Th2 response | 54 |
↓, decreased; ↑, increased; AD, atopic dermatitis; BNP, brain natriuretic peptide; DC, dendritic cell; DRG, dorsal root ganglion; EDC, epidermal differentiation complex; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; GM‐CSFR, granulocyte‐macrophage colony‐stimulating factor receptor; GRP, gastrin‐releasing peptide; IL, interleukin; ILC2, type 2 innate lymphoid cells; MOA, mechanism of action; NKB, neurokinin B; OSMR, oncostatin M receptor; PGD2, prostaglandin D2; ST2, stromal cell line; TNF, tumor necrosis factor; TRPA, transient receptor potential ankyrin; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor.